The objective of this study is to isolate and identify both metabolically and hydrolytically formed products present in ocular tissues of rabbits after topica administraiion of antiviral compounds. The isolated metabolic and hydrolytic products will be tested for toxcity and antiviral activity in tissue cultures of corneal epithelial cells and by perfusion to rabbit corneas. The three antiviral thymidine analogues to be investigated during this study will be 5-trifluoromethyl-2'-deoxyuridine (F3TdR), 5-iodo-5' -amino-2'5'-dideoxyuridine (AIU), and 5-iodo-2'-deoxyuridine (IDU). The metabolism and hydrolysis of thse thymidine analogues will be studied in uninfected rabbits and rabbits with epithelial herpetic keratitis. Tritium label antivials will be topically administered, the animals will be rested sacrificed, and the eyes enucleated for study. Tritium labeled thymidine will be given to rabbits from both experimental groups. These data will serve as the standard of comparison. Eyes from each experimental group wll be fixed for autoradiography in order to localize the radioactive compounds present in cellular nucleotide pools and nucleic acid fractions will be isolated by thin layer and column chromatography. The metabolically and hydrolytically formed products will be identified by thin layer chromatography and spectrophotometry. In the final phase of the study key enzymes believed to contribute to the metabolism of thymidine analogues by ocular tissues will be assayed. The data obtained from this study will allow us to determine which enzymes and what physical properties of ocular tissue contribute to the metabolism and hydrolysis of thymidine analogues. A more rational approach to the chemotherapy of viral disease which effect ocular tissue can be developed, once the factors which influence the stability of these antivirals are studied in detail.